Researchers reject vitamin D role in macular degeneration

Vitamin D does not appear to play a role age-related macular degeneration (AMD), researchers say.

Analyzing data from the European Eye Study, Gareth J. McKay, PhD, of Queen’s University in Belfast, United Kingdom, and colleagues in 7 countries in Europe found no meaningful association between serum 25-hydroxy vitamin D (25(OH)D) and AMD. They published the finding in Ophthalmology.

Though they identified an association between vitamin D deficiency and neovascular AMD, the researchers discounted it because of the possibility of confounding factors.

Vitamin D plays a vital role in multiple systems, including calcium homeostasis, immune response and insulin metabolism. 

Human skin produces the vitamin after exposure to ultraviolet B light, and it is found in a few foods, most notably oily fish. 

However, many Europeans do not spend a significant amount of time in sunlight or eat significant amounts of fish, and about 13% are deficient in 25(OH)D, the researchers wrote.

Genetic factors, can also influence serum vitamin D levels; previous research has identified single nucleotide polymorphisms (SNPs) in several genes related to uptake and metabolism of the nutrient.

Researchers have speculated that vitamin D supplements might reduce the risk of many diseases. While the evidence has been mixed, some studies, including meta-analyses of randomized controlled trials, have suggested it can reduce all-cause mortality.

It is thought that vitamin D could affect AMD because it has anti-inflammatory effects and AMD results from inflammation. Also, vitamin D may reduce the risk of diabetes and cardiovascular disease, both of which increase the risk of AMD.

Mixed research

So far the research in this area has been mixed, with some studies finding an association between AMD and serum vitamin D levels and others not. For example, the US National Health and Nutrition Examination III survey found that lower 25(OH)D levels were associated with early AMD. At the same time, the Korean National Health and Nutrition study found no association between vitamin D levels and early or late AMD.

McKay and colleagues analyzed vitamin D data from the European Eye Study, which recruited 4753 people aged 65 and older from Bergen, Norway; Tallinn, Estonia; Belfast, United Kingdom; Paris, France; Verona, Italy, Thessaloniki, Greece; and Alicante, Spain.

Of the 4496 people who provided usable blood samples, 2137 had no signs of AMD, 2209 had early AMD, 46 had geographic atrophy and 104 had neovascular AMD.

The mean concentration of 25(OH)D was 49 nmol/l, with a standard deviation of 23 nmol/l. The highest mean seasonally adjusted concentration was in the Bergen center: 63 nmol/l. Concentrations were 20 nmol/l less in Paris, 15 nmol/l less in Tallinn, Belfast, Verona and Thessaloniki and 9 nmol/l less in Alicante.

The researchers found vitamin D deficiency in 21% of the participants, and insufficiency in 32.8%. After adjusting for confounding variables, they found that levels were lower with increasing age, in women, in current smokers, and in people with diabetes.

Levels were higher in people taking fish oil supplements and drinking alcohol at least weekly, and in people with higher ultraviolet B exposures, dietary vitamin D intake, serum cholesterol, and plasma concentrations of ascobate, lutein, or zeaxanthin and retinol.

Vitamin D levels were not associated with any grade of early or late AMD or geographic atrophy.

Neovascular AMD was associated with vitamin D deficiency, with an adjusted odds ratio of 1.27 (95% confidence interval 1.11-1.45, P < 0.0001). But the researchers wrote that since 25(OH)D was measured in stored blood samples collected at the same time as AMD was ascertained, there was a possibility that the neovascular AMD reduced the vitamin D levels rather than the vitamin D deficiency causing neovascular AMD.

Limitations

Also they noted that they had no way to control for such factors as depression, anxiety, low physical activity, diabetic nephropathy and other conditions that might lower vitamin D levels.

They noted also that the small number of early and neovascular AMD cases in their study limited their ability to interpret the findings related to these conditions.

The researchers also looked at 92 SNPs and associations with AMD, analyzing the data by the type of AMD and the participants’ age, sex, and location. After using formulas to reduce the risk of statistical errors, they found that none of the SNPs were associated with any form of AMD.

The results of this study were in agreement with some previous studies, but conflicted with others, including some that found an association between AMD, vitamin D deficiency, and specific SNPs.

“We conclude, therefore, that the hypothesis of a causal association of vitamin D with AMD is not supported by clear evidence,” they wrote.